Inguinal Hernia, Postoperative Pain
Conditions
Keywords
postoperative pain, inguinal hernia, chronic postsurgical pain, cytokine, preemptive analgesia, patients with inguinal hernia scheduled for surgery
Brief summary
Inguinal hernia repair is one of the most frequently performed operations in young men. Persistent pain after inguinal surgery represents a significant cause of disability, occurring in between 15%-35% of cases. In a majority of these patients, their groin pain persisted after a previous hernia repair. The main type of chronic postsurgical pain is neuropathic, caused by injured nerves. One of the principal components in the pathophysiology of postsurgical pain is cytokines, specifically tumor necrosis factor (TNF). In animal studies, injecting TNF inhibitors before nerve injury can reduce pain behaviors and neuropathology. Finding a way to reduce the incidence of postsurgical pain after hernia repair could enhance function, and reduce the need for opioids and other analgesics. The investigators intend to conduct the first randomized, controlled study evaluating whether preemptive administration of a tumor necrosis inhibitor can reduce postoperative pain and opioid consumption after hernia repair. This is important because the degree and intensity of postsurgical pain is a major predictor for the development of chronic postsurgical pain.
Detailed description
76 patients with an inguinal hernia scheduled for surgical repair will be randomized in a 1:1 ratio to receive either subcutaneous etanercept or saline before skin incision. The study will be double-blind (i.e. neither the surgeon, anesthesiologist, nor the person administering the injection will know which group they were assigned to). Group I will receive 50 mg of subcutaneous etanercept mixed in 1 ml sterile water 90-120 before skin incision. Group II will receive 1 ml of sterile water 90-120 before skin incision. The anesthesia and surgical procedures will be standardized. For the next 24 hours, patients will keep a q4 hour pain diary recording their average pain on a 0-10 numerical rating scale. They will also record the number of Percocet tablets they took. All patients will be seen 1 month after their surgery, where their average pain score, work status, and analgesic intake (if any) will be recorded. Patients will then be followed with a telephone follow-up 3, 6 and 12-months post-procedure, where the same variables will be recorded.
Interventions
DRUGEtanercept
50 mg subcutaenous preoperatively
DRUGSaline
Given subcutaneously preoperatively
Sponsors
Walter Reed Army Medical Center
John P. Murtha Neuroscience and Pain Institute
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Demonstrable hernia evident using ultrasound, computed tomography, or on physical exam. 2. Pt scheduled for unilateral inguinal hernia repair. 3. Symptoms present for \< 6 months.
Exclusion criteria
1. Non-elective surgery. 2. Previous hernia repair at the same site, or surgery near the site of the hernia. 3. Demyelinating neurological disease. 4. Current or recent (\< 6 years) history of substance abuse. 5. Pregnancy, which will be ruled out by a urine pregnancy test in women of childbearing age. 6. Pre-existing untreated psychiatric condition that could preclude an optimal treatment response (e.g. untreated posttraumatic stress disorder). 7. Unstable medical condition (e.g. unstable angina or congestive heart failure or severe). 8. Rheumatoid arthritis, or other systemic conditions that might respond to TNF inhibitors. 9. Pt is immunosuppressed or is taking other drugs (e.g. corticosteroids) that might suppress the immune system. 10. Systemic infection. 11. Any opioid analgesics within 48 hours of skin incision. 12. Any use of tricyclic antidepressants, serotoninin-norepinephrine reuptake inhibitors, or anticonvulsants within 72 hours of skin incision.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale Pain Score | 24 hours | 0-10 pain score through 24-hours post-surgery. 0 is no pain and 10 is the worse pain imaginable. The primary outcome reported measure is the average of 4 scores, each comprised of 6-hour time intervals during the 24hour period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analgesic Usage | 24 hours | Number of oxycodone/ acetaminophen tablets consumed through 24 hours post-surgery |
| Chronic Post-surgical Pain | Up to 12 months | Patients with persistent post-surgical pain |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Etanercept 50 mg preoperatively
Etanercept : 50 mg subcutaenous preoperatively | 34 |
| Group 2 Subcutaneous saline preoperatively
Saline : Given subcutaneously preoperatively | 43 |
| Total | 77 |
Baseline characteristics
| Characteristic | Group 2 | Group 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 18 Participants | 8 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 2.8 | 55.4 years STANDARD_DEVIATION 3.1 | 57.9 years STANDARD_DEVIATION 2.9 |
| Region of Enrollment United States | 43 participants | 34 participants | 77 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 40 Participants | 31 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 43 |
| serious Total, serious adverse events | 0 / 34 | 0 / 43 |
Outcome results
Primary
Numerical Rating Scale Pain Score
0-10 pain score through 24-hours post-surgery. 0 is no pain and 10 is the worse pain imaginable. The primary outcome reported measure is the average of 4 scores, each comprised of 6-hour time intervals during the 24hour period.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Numerical Rating Scale Pain Score | 3.3 units on a scale | Standard Deviation 1.9 |
| Saline | Numerical Rating Scale Pain Score | 3.9 units on a scale | Standard Deviation 2.3 |
Secondary
Analgesic Usage
Number of oxycodone/ acetaminophen tablets consumed through 24 hours post-surgery
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Analgesic Usage | 4.0 tablets | Standard Deviation 2.8 |
| Saline | Analgesic Usage | 5.8 tablets | Standard Deviation 4.2 |
Secondary
Chronic Post-surgical Pain
Patients with persistent post-surgical pain
Time frame: Up to 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept | Chronic Post-surgical Pain | 5 participants |
| Saline | Chronic Post-surgical Pain | 5 participants |